Yu Xiang George Kong

Impaired Complex-I-Linked Respiration and ATP Synthesis in Primary Open-Angle Glaucoma Patient Lymphoblasts

PURPOSE Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. METHODS Using similar methodology to that previous applied to Lebers hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). RESULTS POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. CONCLUSIONS POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.

Gaze Behavior among Experts and Trainees during Optic Disc Examination: Does How We Look Affect What We See?

PURPOSE The authors compared the visual gaze behaviors of glaucoma subspecialists with those of ophthalmology trainees during optic disc and retinal nerve fiber layer (RNFL) examination. METHODS Seven glaucoma subspecialists and 23 ophthalmology trainees participated in the project. Participants were shown eight glaucomatous optic disc images with varied morphology. Eye movements during examination of the optic disc photographs were tracked. For each disc image, graders were asked to assign a presumptive diagnosis for probability of glaucoma. There was no time restriction. RESULTS Overall, trainees spent more time looking at disc images than glaucoma subspecialists (21.3 [13.9-37.7] vs. 16.6 [12.7-19.7]) seconds; median [interquartile range (IQR)], respectively; P < 0.01) and had no systematic patterns of gaze behavior, and gaze behavior was unaltered by disc morphology or topographic cues of pathology. Experienced viewers demonstrated more systematic and ordered gaze behavior patterns and spent longer times observing areas with the greatest likelihood of pathology (superior and inferior poles of the optic nerve head and adjacent RNFL) compared with the trainees. For discs with focal pathology, the proportion of total time spent examining definite areas of pathology was 28.9% (22.4%-33.6%) for glaucoma subspecialists and 13.5% (12.2%-19.2%) for trainees (median [IQR]; P < 0.05). Furthermore, experts adapted their viewing habits according to disc morphology. CONCLUSIONS Glaucoma subspecialists adopt systematic gaze behavior when examining the optic nerve and RNFL, whereas trainees do not. It remains to be elucidated whether incorporating systematic viewing behavior of the optic disc and RNFL into teaching programs for trainees may expedite their acquisition of accurate and efficient glaucoma diagnosis skills.

A Comparison of Perimetric Results from a Tablet Perimeter and Humphrey Field Analyzer in Glaucoma Patients

Purpose To determine the correlation between the perimetric outcomes from perimetry software Melbourne Rapid Fields (MRF) run on an Apple iPad tablet and those from the Humphrey Field Analyzer (HFA). Methods The MRF software was designed with features including variable fixation and fast thresholding using Bayes logic. Here, we report a cross-sectional study on 90 eyes from 90 participants: 12 had normal optic nerves and 78 had glaucoma with various degrees of visual field loss (41 mild and 37 moderate-severe). Exclusion criteria were patients with worse than 20/40 vision or recent intraocular surgery. The visual field outcomes of MRF were compared against those returned from the HFA 24-2 SITA standard. Participants were tested twice on the MRF to establish test–retest repeatability. Results The test durations were shorter on MRF than HFA (5.7 ± 0.1 vs. 6.3 ± 0.1 minutes, P < 0.001). MRF showed a high level of concordance in its outcomes with HFA (intraclass coefficient [ICC] = 0.93 for mean defect [MD] and 0.86 for pattern deviation [PD]) although the MRF tended to give a less negative MD (1.4 dB bias) compared with the HFA. MRF also showed levels of test–retest reliability comparable to HFA (ICC = 0.93 for MD and 0.89 for PD, 95% limits of agreement −4.5 to 4.3 dB). Conclusion The perimetry results from the MRF have a strong correlation to the HFA outcomes. MRF also has test–retest reliability comparable to HFA. Translational Relevance Portable tablet perimetry may allow accurate assessment of visual field when standard perimetry machines are unavailable or unsuitable.

Surgical outcomes of trabeculectomy and glaucoma drainage implant for uveitic glaucoma and relationship with uveitis activity

This study provides ophthalmologists who manage uveitic glaucoma with important information on factors that can affect the success of surgical management of this challenging disease.

Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual Reality Goggles: A Pilot Study

Purpose To evaluate the use of smartphone-based virtual reality to objectively assess activity limitation in glaucoma. Methods Cross-sectional study of 93 patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire – Utility Index (VFQ-UI) were collected. Mean age was 67.4 ± 13.2 years; 52.7% were male; 65.6% were driving. A smartphone placed inside virtual reality goggles was used to administer the Virtual Reality Glaucoma Visual Function Test (VR-GVFT) to participants, consisting of three parts: stationary, moving ball, driving. Rasch analysis and classical validity tests were conducted to assess performance of VR-GVFT. Results Twenty-four of 28 stationary test items showed acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven of 12 moving ball test items showed acceptable fit (person separation 3.05, targeting 0). No driving test items showed acceptable fit. Stationary test person scores showed good criterion validity, differentiating between glaucoma severity groups (P = 0.014); modest convergence validity, with mild to moderate correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in both eyes (R = 0.243–0.381); and suboptimal divergent validity. Multivariate analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were associated with worse stationary test person scores. Conclusions Smartphone-based virtual reality may be a portable objective simulation test of activity limitation related to glaucomatous visual loss. Translational Relevance The use of simulated virtual environments could help better understand the activity limitations that affect patients with glaucoma.

Sight-threatening complications of cosmetic iris implants: Letter to the Editor

We present a severe sight-threatening complication from cosmetic intraocular iris implantation, highlighting the dangers of iris implants and medical tourism. Intraocular iris implants are single-piece silicone prostheses implanted in the anterior chamber. These devices were initially developed for the treatment of aniridia, however, more recently these devices have been marketed as a cosmetic procedure to individuals who wish to surgically change their eye colour.

Herpes simplex uveitis as a cause of persistent high intraocular pressure after cataract surgery.

A 63-year-old man presented in August 2015 with a 12-day history of persistent high intraocular pressure (IOP) in his right eye (RE) following uncomplicated phacoemulsification surgery. He had been undergoing 3years of monthly ranibizumab injections for choroidal neovascularization complicating presumed acute multifocal placoid pigment epitheliopathy diagnosed in 1990. Prior to his cataract surgery, he had normal IOP; the surgery was uneventful, and peri-operative intracameral cefazolin and subconjunctival dexamethasone were administered. On the first postoperative day (day 1), his RE IOP was 52mmHg with a clear cornea, 1+ cells in the anterior chamber and a quiet vitreous. Oral acetazolamide (250mg) four times daily (QID) and topical latanoprost 0.005% nocte were commenced in addition to routine topical dexamethasone 0.1% QID and chloramphenicol 0.5% QID. Despite the addition of topical brimonidine 0.2% twice daily (BD) and laser peripheral iridotomy, the IOP remained 35mmHg by day 11 when he was referred to our institution. At this presentation, his best corrected visual acuity was 6/6 in his RE (left 6/36), and his IOPs were 45mmHg (RE) and 16mmHg (left eye). Both corneas were clear other than right old-pigmented keratic precipitates inferiorly. There was 3+ flare and a few cells in the anterior chamber, and the only iris transillumination was related to his bilateral peripheral iridotomies. Gonioscopy showed grade 4 open angles throughout, with some pigmentation but no peripheral anterior synechiae. There was no retained lens material. Both optic discs were medium-sized with cup :disc ratios of 0.5, and there was no vitritis or posterior uveitis. Retained viscoelastic was unlikely at this stage, and the dexamethasone drops were replaced with diclofenac 0.1% QID to eliminate the possibility of a steroid response. Furthermore, topical brinzolamide 1%-timolol 0.5% BD was added, the acetazolamide was increased to 500mgQID and superior 180 degrees of selective laser trabeculoplastywas applied; 2days later, an inferior 180° of selective laser trabeculoplasty was applied, pilocarpine 1% QID added and latanoprost 0.005% changed to bimatoprost 0.03%. As the IOP remained elevated at 42mmHg, pilocarpine 1% was ceased to exclude a paradoxical response. However, his right IOP continued to rise, reaching 51mmHg, and he was admitted for intravenous mannitol. His anterior chamber remainedunchangedwith trace cells, andhis cornea remained clear. At this point, an urgent fornix-based trabeculectomy was performed, with subconjunctival application of Mitomycin C 0.2mg/mL for 2min and intravitreal bevacizumab to treat his choroidal neovascularization; thin sclera was noted. An intraoperative sample of aqueous humourwas positive for an active herpes simplex virus 1 (HSV-1) infection on polymerase chain reaction testing, and a course of oral acyclovir (400mg five times daily) was commenced, in addition to routine topical post-trabeculectomy medications. Over the subsequent 3weeks, the patient’s IOP was stabilized with routine post-trabeculectomy care including subconjunctival 5-fluoro-uracil injections and bleb massage. The acyclovir was reduced to a prophylactic dose of 400mg BD. Following his trabeculectomy surgery, the patient continued his usual regimen of monthly intravitreal ranicizumab. At 2-months post-trabeculectomy, his IOP was 18mmHg, and his best corrected visual acuity was 6/6. Surgical traumahas beenknown to trigger new-onset HSVkeratitis and following penetrating keratoplasty, this is akeycauseof graft failure. Topical immunosuppressive therapy and postoperative inflammation are proposed triggers for HSV reactivation. Reactivation of HSV keratitis after cataract surgery is rarely reported, however, and unlike the three cases reported by Barequet et al in which all patients had early postoperative corneal changes and the appearance of a dendritic epithelial ulcer, or Patel et al’s case of a patient presenting at day 5 post-surgery with corneal and eyelid HSV lesions, our case is unique in that there were no corneal or iris signs to point towards a viral cause. Previous retrospective series on HSV anterior uveitis have found that the majority of cases have active keratitis or scarring, or iris abnormalities such as atrophy or distortion, and 50% have elevated IOP. Clues that may have pointed to a viral cause include the markedly high IOP despite minimal uveitis and the presence of old keratic precipitates in the eye; however, these may have been related to previous episodes of posterior uveitis. The trabeculectomy surgery afforded an opportunity to simultaneously obtain an aqueous sample. Aqueous humour polymerase chain reaction confirmation of HSV infection prior to commencing antiviral medication is advised in order to guide treatment of the acute episode and subsequent conditions that may occur such as retinitis, even if surgery is not indicated. In conclusion, we suggest that reactivation of HSV uveitis should be considered in cases of unexplained Competing/conflicts of interest: None.